Patent CA-2850145-C (CA)
Title: Guanides as cell entry promoting agents
Inventor: GOOD LIAM
IPC: C12N5/00
Filed: 2012-10-11
Granted: 2021-02-16
Abstract: A method for promoting entry of an agent (introduced agent) into a cell, the method comprising the step of complexing the introduced agent in the presence of an entry- promoting agent and then exposing to cells, wherein the entry-promoting agent comprises a linear and/or branched or cyclic polymonoguanide/polyguanidine, polybiguanide, analogue or derivative thereof according to the following Formula 1a &b. The method also provides a means for formation of nanoparticles formed between the entry promoting agent and the introduced agent. wherein: "n", refers to number of repeating units in the polymer, and n can vary from 2 to 1000, for example from 2 or 5 to 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800 or 900; G1 and G2 independently represent a cationic group comprising biguanide or guanidine, wherein L1, and L2 are directly joined to a Nitrogen atom of the guanide; L1 and L2 are linking groups between the G1 and G2 cationic groups in the polymer and independently represent an aliphatic group containing C1-C40 carbon atoms, for example an alkyl group such as methylene, ethylene, propylene, C4, C5, C6, C7, C8, C9 or C10; C1-C10, -C20, - C30, -C40, -C50 -C60 -C70, -C80, -C90, -C-100, -C110, -C120, -C130 or -C140, alkyl; or a C1-C140 (for example C1 , C2,C3, C4, C5, C6, C7, C8, C9 or C10; C1-C10, -C20, -C30, -C40, -C50 -C60, -C70, -C80, - C90, -C100, -C110, -C120, -C130o or -C140), cycloaliphatic, heterocyclic, aromatic, aryl, alkylaryl, arylalkyl, or oxyalkylene radical; or a polyalkylene radical optionally interrupted by one or more, preferably one, oxygen, nitrogen or sulphur atoms, functional groups or saturated or unsaturated cyclic moiety; N and G3 are optional end groups; X can be either present or absent; L3, L4 and X are linking groups between the G4 and G5 cationic groups in the polymer and independently represent an aliphatic group containing C1-C140 carbon atoms, for example an alkyl group such as methylene, ethylene, propylene, C4, C5, C6, C7, C8, C9 or C10; C1-C10, -C20, -C30, - C40, -C50 -C60, -C70, -C80, -C90, -C100, -C110, -C120, -C130 or -C140, alkyl; or L3 and L4 and X can independently be C1-C140 (for example C1,C2, C3, C4, C5, C6, C7, C8, C9 or C10; C1-C10, -C20, -C30, -C40, -C50 -C60, -C70, -C80, -C90, -C100, -C110, -C120, -C130 or -C140), cycloaliphatic, heterocyclic, aromatic, aryl, alkylaryl, arylalkyl, oxyalkylene radicals; or a polyalkylene radical optionally interrupted by one or more, preferably one, oxygen, nitrogen or sulphur atoms, functional groups as well as saturated or unsaturated cyclic moiety; "G4" and "G5" are cationic moieties and can be same or different, and at least one of them is a biguanidine moiety or carbamoylguanidine, and the other moiety may be biguanidine or carbamoylguanidine or amine; and cationic moieties G4 and G5 do not contain single guanidine groups. The entry-promoting agent may comprise homogeneous or heterogeneous mixture of one or more of agents arising from formulae 1 a and b, for example polyhexamethylene biguanide (PHMB), polyhexamethylene monoguanide (PHMG), polyethylene biguanide (PEB), polytetramethylene biguanide (PTMB), polyethylene hexamethylene biguanide (PEHMB), polymethylene biguanides (PMB), poly(allylbiguanidnio-co-allylamine), poly(N- vinylbiguanide), polyallybiguanide.